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Biotech to Design Disease-Blocking Drugs, Gains $75M

Chemical atom model

(Fernando Zhiminaicela, Pixabay.

1 May 2023. A new company that says it can stop disease-causing proteins from forming in cells began public operations today, and is raising $75 million in its first venture round. Initial Therapeutics Inc. in South San Francisco emerged from stealth mode after three years, spun-off from research labs at three University of California campuses.

Initial Therapeutics is a biotechnology enterprise formed by life science venture investor Apple Tree Partners in New York. The company says its process, called selective termination of protein synthesis or STOPS, designs small molecule or low molecular weight treatments that can modify the synthesis of proteins in cells. Initial Therapeutics says the technology recognizes protein synthesis in its early stages, when a linear sequence of components forms but before the full three-dimensional protein takes shape. The company says these interventions take place in the ribosome, where amino acids are matched and linked together into protein chains, following instructions from messenger RNA or mRNA.

Apple Tree Partners says it formed Initial Therapeutics to commercialize research from the labs of biochemistry and biomedical engineering professor Jamie Cate at UC-Berkeley, pharmacy science professor Brian Paegel at UC-Irvine, and pharmacology and chemistry professor Kevan Shokat at UC-San Francisco. Cate and associates at UC-Berkeley study protein synthesis in the ribosome, while Shokat’s lab discovers enzymes for better understanding protein signaling patterns, and Paegel’s lab designs microfluidic or lab-on-a-chip tools for analyzing the structure of proteins to find vulnerabilities in disease targets that up now are considered difficult to address.

Stalls formation of peptide chains

“We started Initial Therapeutics,” says Cate in a company statement, “to go after therapeutically important proteins that no one has been able to target successfully.” In a 2019 paper, Cate and colleagues demonstrated a small molecule compound that selectively binds to the ribosome and stalls formation of peptide chains in cells. This work, says Initial Therapeutics, is coupled with a large-scale ribosome screening system made up of miniaturized microfluidics devices from the Paegel lab.

“Where other drug modalities involve recognition of the three-dimensional shape of the protein,” notes Shokat, “Initial’s modality recognizes the primary linear sequence.” Shokat adds, “Some proteins don’t have ligandable pockets, but a linear sequence, that’s in everything. Initial’s bespoke platform allows us to go into the ribosome, the machinery of mRNA translation, in a selective way that has never before been technically possible.”

Spiros Liras, a venture partner at Apple Tree and founding CEO of Initial Therapeutics says, “Initial grew out of conversations between Jamie, Kevan, Brian, and me about work we had each been doing in these intersecting areas of protein synthesis kinetics, ribosome profiling, rapid chemistry, etc., and how we could collaborate to build something new to expand on the idea of selectively modulating protein translation, which we all saw as potentially transformative.”

Initial Therapeutics is raising $75 million in its first venture funding round, with Apple Tree Partners listed as the only investor. According to Crunchbase, Apple Tree Partners also provided Initial Therapeutics $3.8 million in seed funds in July 2020.

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